scholarly journals Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model

2020 ◽  
Vol 17 (6) ◽  
pp. 847-862
Author(s):  
Hussam Al Hussein ◽  
Hamida Al Hussein ◽  
Carmen Sircuta ◽  
Ovidiu S. Cotoi ◽  
Ionela Movileanu ◽  
...  
Keyword(s):  
Ovine Model ◽  
Orthotopic Implantation ◽  
Animal Care

CONCEPTION AND VALIDATION OF A REFLUX LARYNGITIS MODEL INNEWBORN LAMBS

2008 ◽  
Vol 31 (4) ◽  
pp. 6
Author(s):  
A-M Carreau ◽  
H Patural ◽  
A Doueik ◽  
P-H Fortier ◽  
J P Praud
Keyword(s):  
Weight Gain ◽  
Gastric Juice ◽  
Histological Study ◽  
Ovine Model ◽  
Preliminary Results ◽  
Surgical Instrumentation ◽  
Clinical Observations ◽  
Study Results ◽  
Reflux Laryngitis ◽  
Histological Characteristics

Background: Daily clinical observations and a recent study (D Vermeylen et al., 2004) suggest that reflux laryngitis (RL) is involved in apneas/ bradycardias of the newborn. The aim of this study is to develop and tovalidate a unique RL model in newborn lambs to test the assumption that a RL provokesan increase in apneas/ bradycardias/ desaturations observed within thelaryngeal chemoreflexes induced by the contact of a liquid with the larynx. Methods: A surgical instrumentation was performed on the first day of life, which included the insertion of a transcutaneous esophageal catheter in order to allow instillation of a gastric juice surrogate (HCl +pepsin at pH 2) directly on the larynx. The 2 ml-instillations were made 3 times per day for 6 consecutive days. At day 9-10 laryngeal chemoreflexes were induced during sleep. The larynx was removed at the time of necropsy to grade inflammation by a histological study. Results: Lambs in which a RL was induced (n = 4) presented characteristic signs of RL: cough, weak bleat, reduction in weight gain. Preliminary histological analyses showed a characteristic laryngeal inflammation. Preliminary results showing that apneas and oxygen desaturations seem more prominent in RL lambs than controls provided further validation ofour RL model. Conclusion: The ovine model developed in this study presents theclinical and histological characteristics of RL observed in newborns. Preliminary results suggesting that a RL increases apneas/bradycardias/desaturations when a liquid is in contact with laryngealmucosa in the newborn must be confirmed. Supported by: CIHR, FRSQ, Foundation of stars.

Carbon Monoxide and Pulmonary Circulation in an Ovine Model

1992 ◽  
Vol 13 (6) ◽  
pp. 623-627 ◽  
Author(s):  
J. L. Theissen ◽  
H. M. Loick ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
D. L. Traber
Keyword(s):  
Carbon Monoxide ◽  
Pulmonary Circulation ◽  
Ovine Model

Learning organizations and animal care programs in the absence of appropriate national legislation

2021 ◽  
pp. 002367722110192
Author(s):  
Lazara Martínez-Muñoz
Keyword(s):  
Latin American ◽  
Laboratory Animal ◽  
Management Education ◽  
Education Programs ◽  
Animal Science ◽  
Five Disciplines ◽  
Research Facilities ◽  
Animal Care ◽  
Latin American Countries ◽  
Working Method

The absence, in many nations, of appropriate and corresponding legislation for the protection of experimental animals as well as continual management education programs, significantly affects the inclusion and recognition of experimental results, worldwide. For more than a decade, researchers from Latin American countries have unsuccessfully struggled to get proper legislation. Until today, not many effective results have been seen. After reviewing previous literature and carefully analyzing the available methodologies and practical examples, this paper aims at redesigning the actions and strategies of the members of the research facilities to implement an effective laboratory animal care and use program, and permit the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) accreditation, independent of national legislative network .This paper also suggests a domestic working method for the teamwork to assume international harmonized legislation, through the application of the Five Disciplines stated by Senge, as methodological process linked with laboratory animal science as scientific background.

scholarly journals Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 594
Author(s):  
Amy L. Lesneski ◽  
Payam Vali ◽  
Morgan E. Hardie ◽  
Satyan Lakshminrusimha ◽  
Deepika Sankaran
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Oxygen Saturation ◽  
Ductus Arteriosus ◽  
Neonatal Resuscitation ◽  
Meconium Aspiration Syndrome ◽  
Ovine Model ◽  
Neurodevelopmental Outcomes ◽  
Meconium Aspiration ◽  
Blood Flows

Neonatal resuscitation (NRP) guidelines suggest targeting 85–95% preductal SpO2 by 10 min after birth. Optimal oxygen saturation (SpO2) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (QPA), carotid (QCA)and ductal (QDA) blood flows between standard (85–94%) and high (95–99%) SpO2 targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85–94%) or high (95–99%) SpO2 targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO2 targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO2 target (7.4 (4.4–10.8) min) compared to standard SpO2 target (31.5 (21–66.2) min, p = 0.03). QPA was significantly higher during the first 10 min after birth with higher SpO2 target. At 60 min after birth, the QPA, QCA and QDA were not different between the groups. To conclude, targeting SpO2 of 95–99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase QPA but no differences were observed at 60 min. Clinical studies comparing low and high SpO2 targets assessing hemodynamics and neurodevelopmental outcomes are warranted.

112 Rational design of chimeric antigen receptor T cells against glypican 3 decouples toxicity from therapeutic efficacy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A124-A124
Author(s):  
Letizia Giardino ◽  
Ryan Gilbreth ◽  
Cui Chen ◽  
Erin Sult ◽  
Noel Monks ◽  
...  
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Single Chain ◽  
High Affinity ◽  
Car T Cells ◽  
Car T ◽  
Animal Care ◽  
Cytotoxic Function

BackgroundChimeric antigen receptor (CAR)-T therapy has yielded impressive clinical results in hematological malignancies and it is a promising approach for solid tumor treatment. However, toxicity, including on-target off-tumor antigen binding, is a concern hampering its broader use.MethodsIn selecting a lead CAR-T candidate against the oncofetal antigen glypican 3 (GPC3), we compared CAR bearing a low and high affinity single-chain variable fragment (scFv,) binding to the same epitope and cross-reactive with murine GPC3. We characterized low and high affinity CAR-T cells immunophenotype and effector function in vitro, followed by in vivo efficacy and safety studies in hepatocellular carcinoma (HCC) xenograft models.ResultsCompared to the high-affinity construct, the low-affinity CAR maintained cytotoxic function but did not show in vivo toxicity. High-affinity CAR-induced toxicity was caused by on-target off-tumor binding, based on the evidence that high-affinity but not low-affinity CAR, were toxic in non-tumor bearing mice and accumulated in organs with low expression of GPC3. To add another layer of safety, we developed a mean to target and eliminate CAR-T cells using anti-TNFα antibody therapy post-CAR-T infusion. This antibody functioned by eliminating early antigen-activated CAR-T cells, but not all CAR-T cells, allowing a margin where the toxic response could be effectively decoupled from anti-tumor efficacy.ConclusionsSelecting a domain with higher off-rate improved the quality of the CAR-T cells by maintaining cytotoxic function while reducing cytokine production and activation upon antigen engagement. By exploring additional traits of the CAR-T cells post-activation, we further identified a mechanism whereby we could use approved therapeutics and apply them as an exogenous kill switch that would eliminate early activated CAR-T following antigen engagement in vivo. By combining the reduced affinity CAR with this exogenous control mechanism, we provide evidence that we can modulate and control CAR-mediated toxicity.Ethics ApprovalAll animal experiments were conducted in a facility accredited by the Association for Assessment of Laboratory Animal Care (AALAC) under Institutional Animal Care and Use Committee (IACUC) guidelines and appropriate animal research approval.

scholarly journals 344 The Ag Guide serves as a primary standard for animal scientists and AAALAC accreditation of Ag research programs

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 71-72
Author(s):  
Janeen Salak-Johnson
Keyword(s):  
Animal Welfare ◽  
Primary Standard ◽  
Animal Research ◽  
Third Party ◽  
Best Interests ◽  
Professional Judgment ◽  
High Quality ◽  
Accreditation Program ◽  
Agricultural Animal ◽  
Animal Care

Abstract Institutions that engage in animal research and production must ensure that high standards of animal care and use meet expectations of society while being ethical stewards of the animals they use in research. In order to achieve engagement in best practices, the Ag Guide is the most appropriate standard for assessing agricultural animals used in research and teaching. The Ag Guide minimizes the potential to overuse performance standards while enhancing the ability to appropriately address specific performance-derived exceptions to situations for which they have been validated. The primary objectives of the standards established in the Ag Guide are well-aligned with the goals of the AAALAC International accreditation program. The Ag Guide provides scientifically-sound, performance-based approaches to animal care and housing, which meet the expectations of AAALAC’s accreditation program. AAALAC provides a third-party peer review of all facets of the animal care and use program that serves as an effective mechanism to ensure institutions meet the standards of the Ag Guide. The process is designed to help identify the strengths and weaknesses of the program to ensure high-quality scientific outcomes and a high level of animal welfare. AAALAC accreditation program for agricultural animal research program is built on the cornerstone of the Ag Guide standards and connects science and responsible animal care. AAALAC accreditation promotes a comprehensive, institutionally supported program with a commitment to continuous improvement, humane and ethical animal care resulting in high-quality animal welfare, and scientific validity. AAALAC takes the position that, in accredited programs, the housing and care for agricultural animals should meet the standards that prevail on a high-quality, well-managed farm and the Ag Guide serves as this foundation. Therefore, the use of the Ag Guide for agricultural animal programs ensures a review that is based on science, professional judgment, and the best interests of the animal.

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